PRR12-Related Neuroocular Syndrome: Disease Characteristics Report

Executive summary and evidence scope

PRR12-related neuroocular syndrome is an ultra-rare, autosomal-dominant developmental disorder caused primarily by heterozygous loss of PRR12 function. Its defining combination is developmental impairment—often intellectual disability—with highly variable congenital ocular abnormalities and frequent cardiac, renal, growth, and hypotonia phenotypes. The principal disease-defining study remains Chowdhury et al., published in Genetics in Medicine in July 2021 (accepted 11 February 2021; DOI: 10.1038/s41436-021-01129-6). It assembled 24 individuals, aged 5 months–36 years, including 11 females and 13 males. Focused searches did not identify a disease-specific 2023–2024 cohort, natural-history study, clinical guideline, or therapeutic trial; therefore, “current understanding” still rests predominantly on this 2021 cohort and earlier ocular case reports. A PMID was not recoverable from the retrieved material, so the DOI is supplied rather than an uncertain PMID. (chowdhury2021haploinsufficiencyofprr12 pages 2-2, chowdhury2021haploinsufficiencyofprr12 pages 1-2)

The authors’ abstract-level conclusion is directly applicable: “These findings support PRR12 haploinsufficiency as a cause for a novel disorder with a wide clinical spectrum marked chiefly by neurodevelopmental and eye abnormalities.” (chowdhury2021haploinsufficiencyofprr12 pages 1-2)

Table: This table condenses the current disease-defining evidence for PRR12-related neuroocular syndrome into knowledge-base-ready fields. It separates observed human findings from mechanistic hypotheses and highlights where evidence is still lacking.

1. Disease information

Definition and names

The preferred descriptive name is PRR12-related neuroocular syndrome. Literature alternatives include PRR12-related disorder, PRR12 haploinsufficiency disorder, and neurodevelopmental, eye, and multisystem abnormalities due to PRR12 haploinsufficiency. “Dominant complex microphthalmia due to PRR12 variants” describes the ocular-predominant end of the spectrum rather than every affected person, because 12/24 had no documented structural eye defect. (chowdhury2021haploinsufficiencyofprr12 pages 1-2, chowdhury2021haploinsufficiencyofprr12 pages 6-8)

Identifiers

• Gene: PRR12 (proline rich 12); historical alias KIAA1205.
• Locus: chromosome 19q13.33–q13.41 region; the disease-causing sequence variants are intragenic, while one reported patient had a 3.352-Mb deletion spanning chr19:50,012,428–53,364,114 (hg19) and many additional genes. (chowdhury2021haploinsufficiencyofprr12 pages 3-4, chowdhury2021haploinsufficiencyofprr12 pages 9-10)
• MONDO, Orphanet, disease-specific OMIM, MeSH, ICD-10, and ICD-11 identifiers: no dedicated identifier was verified in the retrieved evidence. A knowledge base should not assign a code without direct database confirmation. Existing ICD/HPO terms can encode component manifestations, but not the molecular syndrome itself.

The evidence is an aggregated disease-level case series, assembled through clinical genetics teams and matchmaking platforms, not a population EHR cohort. A separate PrediXcan analysis used BioVU electronic health records from approximately 25,000 genotyped European Americans, but it examined associations with genetically predicted PRR12 expression and does not establish syndrome prevalence or penetrance. (chowdhury2021haploinsufficiencyofprr12 pages 1-2, chowdhury2021haploinsufficiencyofprr12 pages 8-9)

2. Etiology, risk, and protective factors

The primary cause is a germline heterozygous pathogenic PRR12 alteration, usually arising de novo. The supported mechanism is haploinsufficiency. Truncating and splice variants introduce premature termination codons before the penultimate exon and are predicted to undergo nonsense-mediated mRNA decay. (chowdhury2021haploinsufficiencyofprr12 pages 2-3, chowdhury2021haploinsufficiencyofprr12 pages 2-2)

No environmental, infectious, toxic, lifestyle, occupational, or dietary causal factor has been demonstrated. No protective allele, modifier gene, protective exposure, or gene–environment interaction has been established. Additional diagnoses may modify individual presentations: three cohort members carried other clinically relevant variants, including PIK3CA, KDM6B, and LZTR1 findings, making attribution of every feature to PRR12 uncertain. (chowdhury2021haploinsufficiencyofprr12 pages 8-9, chowdhury2021haploinsufficiencyofprr12 pages 9-10)

3. Phenotypes

The following frequencies are from the 24-person disease-defining cohort and should not be interpreted as population prevalence.

Neurodevelopment

• Developmental impairment: present in all reported sequence-variant cases; 17 had global developmental delay, 3 isolated motor delay, and 4 isolated speech-language delay. Suggested terms: HP:0001263 Global developmental delay, HP:0001270 Motor delay, and HP:0000750 Delayed speech and language development. (chowdhury2021haploinsufficiencyofprr12 pages 2-2)
• Intellectual disability: documented in all 11 evaluable individuals older than seven years, ranging from mild to severe. Suggested term: HP:0001249 Intellectual disability. (chowdhury2021haploinsufficiencyofprr12 pages 2-2)
• Hypotonia: 14/23 (61%), during or beyond the neonatal period. Suggested term: HP:0001252 Hypotonia. (chowdhury2021haploinsufficiencyofprr12 pages 8-9)
• Behavioral observations included ADHD, autism-spectrum features, aggression, repetitive or self-injurious behavior in individual cases, but reliable cohort frequencies were not extractable. No validated behavioral profile is established. (chowdhury2021haploinsufficiencyofprr12 pages 5-6)

Eye and visual system

• Any structural eye abnormality: 12/24 (50%).
• Anophthalmia/microphthalmia: 4/24 (16.7%); all four were female in this small cohort. Suggested terms: HP:0000528 Anophthalmia, HP:0000568 Microphthalmia.
• Coloboma: 7/24 (29%), most often iris but also optic nerve, macula, chorioretina, and lens; HP:0000589 Coloboma and site-specific child terms.
• Visual impairment: 17/22 (77%); HP:0000505 Visual impairment.
• Strabismus: 8/22 (36%); HP:0000486 Strabismus.
• Other reported structures included retinal dysplasia, persistent pupillary membrane, Rieger anomaly, optic-nerve hypoplasia or abnormal shape, retinal pigment-epithelium hypertrophy, ptosis, and nystagmus. Patient 1 had bilateral anophthalmia with absent optic nerves, tracts, and chiasm on MRI. (chowdhury2021haploinsufficiencyofprr12 pages 2-3, chowdhury2021haploinsufficiencyofprr12 pages 6-8)

Eye severity therefore ranges from no apparent structural defect to bilateral anophthalmia and profound visual disability. Four individuals lacked complete ophthalmological assessment, so posterior abnormalities may be under-ascertained. (chowdhury2021haploinsufficiencyofprr12 pages 6-8)

Multisystem findings

• Congenital heart defect: 12/23 (52%): six atrial septal defects, two ventricular septal defects, and three pulmonary stenoses, with one person having two defects. Suggested terms: HP:0001627 Abnormal heart morphology, HP:0001631 Atrial septal defect, HP:0001629 Ventricular septal defect, HP:0001642 Pulmonic stenosis. (chowdhury2021haploinsufficiencyofprr12 pages 6-8)
• Kidney/urinary anomaly: 8/23 (35%), including hydronephrosis, duplicated ureter, and vesicoureteral reflux. Suggested umbrella term: HP:0012210 Abnormal renal morphology, plus the corresponding specific HPO terms. (chowdhury2021haploinsufficiencyofprr12 pages 6-8)
• Failure to thrive: 13/24 (54%); HP:0001508 Failure to thrive.
• Microcephaly: 7/24 (29%); HP:0000252 Microcephaly.
• Cryptorchidism: 5/13 males (38%); HP:0000028 Cryptorchidism.
• Cleft palate: 4/24 (17%); HP:0000175 Cleft palate.
• Intestinal malrotation: 2/24 (8%); HP:0002566 Intestinal malrotation.
• Meckel diverticulum: 1/24 (4%). (chowdhury2021haploinsufficiencyofprr12 pages 8-9, chowdhury2021haploinsufficiencyofprr12 pages 6-8)

Facial findings—wide-set eyes, epicanthal folds, low-set ears, upturned nasal tip, and thin vermilion—each occurred in at least 25%, but the authors found no recognizable gestalt. (chowdhury2021haploinsufficiencyofprr12 pages 8-9, chowdhury2021haploinsufficiencyofprr12 pages 6-8)

No disease-specific EQ-5D, SF-36, PROMIS, educational-attainment, caregiver-burden, or quality-of-life study exists. Nevertheless, intellectual disability, visual impairment, feeding/growth difficulty, and congenital organ disease plausibly impair communication, learning, mobility, and independent functioning; this is clinical inference, not a measured outcome.

4. Genetic and molecular information

The cohort contained 12 frameshift, 6 nonsense, 1 splice-site, 2 missense variants, and one gross deletion. Twenty-one distinct sequence variants were represented. Examples include recurrent c.1521T>G (p.Tyr507) and c.3273delC (p.Lys1092Argfs131), and the missense changes c.3505C>T (p.Arg1169Trp) and c.5909T>C (p.Leu1970Pro). The missense changes had PolyPhen-2 scores of 0.998 and 1.000 but remain less directly supported mechanistically than truncating alleles. (chowdhury2021haploinsufficiencyofprr12 pages 2-2, chowdhury2021haploinsufficiencyofprr12 pages 2-3)

PRR12 is strongly constrained against loss of function: pLI 1.00, observed/expected LOF ratio 0.0 (90% CI 0–0.05), and LOEUF 0.051; its missense Z score was +2.98. These are population-constraint metrics, not patient-specific pathogenicity criteria. Disease alleles are germline; no somatic disease mechanism is reported. (chowdhury2021haploinsufficiencyofprr12 pages 2-2)

The main transcript used was NM_020719.3/ENST00000418929.7. A shorter 1,215-amino-acid, approximately 130-kDa isoform (ENST00000615927.1) omits exons 1–3 and most of exon 4. Eight variants were predicted to spare this short isoform, but phenotype differences between isoform groups were not statistically significant. (chowdhury2021haploinsufficiencyofprr12 pages 2-2, chowdhury2021haploinsufficiencyofprr12 pages 10-11)

No validated modifier gene, methylation episignature, allele-specific expression biomarker, or pathogenic structural rearrangement restricted solely to PRR12 has been established. The large deletion case is informative but confounded by loss of 146 annotated genes, including PPP2R1A. (chowdhury2021haploinsufficiencyofprr12 pages 9-10)

5. Environmental information

Environmental contributors, infectious triggers, smoking, alcohol, diet, exercise, radiation, pollution, and occupational exposures are not implicated. This is a constitutional Mendelian developmental disorder. Standard healthy-lifestyle measures remain appropriate but are not disease-preventive.

6. Mechanism and pathophysiology

Evidence-supported causal chain

1. A heterozygous truncating/splice/deletion allele reduces functional PRR12 dosage, usually through nonsense-mediated decay.
2. PRR12 is a nuclear protein expressed strongly during fetal brain development and in the mouse visual system.
3. Reduced dosage during embryonic development likely disrupts developmental gene regulation in neural, ocular, cardiac, and renal progenitor programs.
4. Abnormal morphogenesis produces congenital ocular and organ defects; altered neural development produces delay, intellectual disability, and hypotonia. Steps 1–2 are supported; steps 3–4 remain a biologically plausible model rather than experimentally proven pathway mapping. (chowdhury2021haploinsufficiencyofprr12 pages 1-2, chowdhury2021haploinsufficiencyofprr12 pages 9-10, chowdhury2021haploinsufficiencyofprr12 pages 2-3)

PRR12 contains two predicted AT-hook DNA-binding domains and is restricted to the nucleus. Coexpression neighborhoods are enriched for transcriptional regulation, chromatin regulators, SET-domain proteins, bromodomain proteins, zinc-finger proteins, and BAH-domain proteins. Candidate interactions with USP7, SOX2, and ESR2 could connect PRR12 to neurodevelopment and eye formation, but the authors emphasize that these interactions and consequences remain experimentally unproven. (chowdhury2021haploinsufficiencyofprr12 pages 10-11)

A useful exact quotation is: “The exact role of PRR12 in transcriptional regulation remains unclear and will require further functional studies to elucidate.” (chowdhury2021haploinsufficiencyofprr12 pages 10-11)

Suggested annotations, all provisional except nuclear localization: GO:0005634 nucleus; GO:0006355 regulation of DNA-templated transcription; GO:0007420 brain development; GO:0001654 eye development; GO:0048856 anatomical structure development; candidate cell types CL:0000047 neuronal stem cell and CL:0000127 astrocyte/other neural lineage terms only where future evidence supports them. No validated metabolic, immune, inflammatory, autophagic, mitochondrial, lipidomic, metabolomic, proteomic, single-cell, spatial-transcriptomic, CRISPR-screen, or multi-omic disease signature is available.

7. Anatomical structures affected

Primary systems are the central nervous system and eye; frequent secondary involvement includes heart, kidney/urinary tract, craniofacial structures, gastrointestinal tract, and male genital tract. Suggested UBERON annotations include UBERON:0000955 brain, UBERON:0000970 eye, UBERON:0000948 heart, and UBERON:0002113 kidney. Ocular disease may involve globe, iris, optic nerve, retina/choroid, macula, lens, and visual pathways. Findings may be unilateral, bilateral, or asymmetric; severe globe defects were not uniformly bilateral. (chowdhury2021haploinsufficiencyofprr12 pages 2-3, chowdhury2021haploinsufficiencyofprr12 pages 6-8)

At the subcellular level, PRR12 localizes to the nucleus (GO:0005634). Specific vulnerable human cell populations have not been established experimentally. Neural progenitor involvement is inferred from developmental expression and poised chromatin observations, not demonstrated by patient single-cell data. (chowdhury2021haploinsufficiencyofprr12 pages 9-10)

8. Temporal development

The disorder is congenital/developmental. Structural eye, heart, kidney, palate, and gastrointestinal abnormalities arise prenatally; hypotonia may be neonatal or persist beyond that period. Developmental delay becomes apparent in infancy or childhood, while intellectual disability is assessable later. The available ages span 5 months–36 years. (chowdhury2021haploinsufficiencyofprr12 pages 2-2, chowdhury2021haploinsufficiencyofprr12 pages 8-9)

There are no defined stages, progression rate, remission pattern, critical treatment window, or prospective natural-history data. Congenital malformations are generally static, whereas developmental capabilities may change with maturation and intervention. Whether retinal, renal, or neuropsychiatric manifestations progress is unknown.

9. Inheritance and population

The pattern is autosomal dominant, predominantly de novo. Recurrence risk for unaffected parents is usually low but not zero because parental germline mosaicism cannot be excluded; an affected individual would theoretically have a 50% transmission risk per pregnancy, subject to currently uncertain penetrance and expressivity. No familial multigenerational series establishes penetrance. Expressivity is clearly variable, especially for ocular severity. (chowdhury2021haploinsufficiencyofprr12 pages 2-2, chowdhury2021haploinsufficiencyofprr12 pages 6-8)

No incidence, prevalence, carrier frequency, founder effect, consanguinity association, ethnic enrichment, geographic concentration, anticipation, or reliable sex ratio exists. The cohort’s 11:13 female-to-male distribution does not demonstrate sex bias. The female-only globe defects are hypothesis-generating because only four such cases occurred. (chowdhury2021haploinsufficiencyofprr12 pages 2-2, chowdhury2021haploinsufficiencyofprr12 pages 6-8)

10. Diagnostics

Diagnosis requires identification of a pathogenic/likely pathogenic heterozygous PRR12 variant or deletion in an appropriate phenotype, followed by segregation testing. Trio exome or genome sequencing is efficient because the phenotype is broad and frequently de novo. Genome sequencing may better detect structural and noncoding variants; chromosomal microarray is appropriate when multiple congenital anomalies suggest a copy-number change. Single-gene sequencing or a neurodevelopmental/anophthalmia–microphthalmia–coloboma panel is reasonable when PRR12 is included. Karyotype/FISH can characterize a suspected translocation but are not first-line for small sequence variants. Mitochondrial and repeat-expansion tests have no disease-specific role. (chowdhury2021haploinsufficiencyofprr12 pages 1-2, chowdhury2021haploinsufficiencyofprr12 pages 9-10)

Baseline phenotyping should include formal pediatric ophthalmology—not merely external inspection—developmental and neurologic assessment, growth/head circumference, echocardiography, renal ultrasound, hearing assessment, and examination for palate, genital, and gastrointestinal anomalies. This is phenotype-directed expert synthesis; no society guideline has yet standardized surveillance. Incomplete ophthalmologic examination demonstrably risks missing posterior defects. (chowdhury2021haploinsufficiencyofprr12 pages 6-8)

Differential diagnoses include SOX2-related anophthalmia, OTX2-related disease, PAX6 disorders, CHD7/CHARGE syndrome, PAX2 renal-coloboma syndrome, and SALL4-related acro-renal-ocular/Okihiro spectrum. PRR12 disease is distinguished molecularly and by its combination of developmental impairment with variable eye, cardiac, renal, and growth findings. (chowdhury2021haploinsufficiencyofprr12 pages 10-11, chowdhury2021haploinsufficiencyofprr12 pages 9-10)

No biochemical assay, circulating biomarker, diagnostic methylation signature, biopsy finding, or validated RNA/proteomic/metabolomic test exists.

11. Outcomes and prognosis

No survival curve, mortality rate, life-expectancy estimate, prospective adult cohort, or prognostic biomarker exists. The oldest reported participant was 36 years, demonstrating survival into adulthood but not normal life expectancy. Morbidity is driven by intellectual/developmental disability, visual impairment, hypotonia, feeding/growth problems, and congenital organ defects. (chowdhury2021haploinsufficiencyofprr12 pages 2-2, chowdhury2021haploinsufficiencyofprr12 pages 6-8)

Recovery of congenital structural defects is not expected, although developmental function and adaptive skills may improve with therapy. Prognosis should be individualized according to visual severity, level of intellectual disability, feeding/growth status, and cardiac/renal disease. These predictors are clinically reasonable but have not been statistically validated for this syndrome.

12. Treatment and current applications

There is no disease-modifying drug, gene therapy, RNA therapy, cell therapy, or PRR12-targeted treatment, and no relevant registered interventional trial was identified. Management is supportive and multidisciplinary:

• early developmental, speech-language, occupational, and physical therapy;
• low-vision services, refractive/amblyopia treatment, and surgical management of strabismus, cataract, glaucoma risk, coloboma complications, or anophthalmic sockets as individually indicated;
• standard cardiology care for septal defects or pulmonary stenosis;
• nephrology/urology care for hydronephrosis, reflux, or duplicated collecting systems;
• nutritional/feeding support and growth monitoring;
• standard treatment of cleft palate, cryptorchidism, and intestinal malrotation;
• behavioral and educational supports.

Suggested NCIT intervention concepts include Genetic Counseling, Physical Therapy, Occupational Therapy, Speech Therapy, Supportive Care, and the appropriate procedure-specific concepts. No response-rate, comparative-effectiveness, adverse-event, pharmacogenomic, or combination-therapy data are available.

13. Prevention

The causal de novo event cannot presently be prevented through lifestyle or vaccination. Primary prevention is therefore limited to reproductive options after molecular diagnosis: genetic counseling, parental testing, prenatal diagnosis, and preimplantation genetic testing. Secondary prevention consists of early molecular diagnosis and prompt identification of ocular, cardiac, renal, feeding, and developmental complications. Tertiary prevention is multidisciplinary surveillance and rehabilitation intended to reduce avoidable visual loss, developmental disability, renal injury, and cardiac morbidity. Population newborn or carrier screening is not supported by current evidence.

14. Other species and natural disease

PRR12 coding sequence is conserved among vertebrates, and developmental mouse expression is strongest in fetal E15 brain relative to adult brain; expression in the mouse visual system has also been reported. However, no naturally occurring PRR12-associated veterinary syndrome, breed predisposition, zoonotic potential, or cross-species transmission is known. (chowdhury2021haploinsufficiencyofprr12 pages 1-2, chowdhury2021haploinsufficiencyofprr12 pages 9-10)

Suggested taxa for comparative work are Homo sapiens (NCBI Taxon 9606), Mus musculus (10090), and Danio rerio (7955). Ortholog-specific NCBI Gene identifiers should be confirmed directly before database loading.

15. Model organisms and research priorities

No published PRR12 knockout/knock-in animal model was identified that demonstrably recapitulates the human neuroocular syndrome. No patient-derived iPSC, organoid, or validated cellular disease model was found. The disease-defining authors explicitly stated that mouse and zebrafish models would be valuable for defining PRR12 function and pathogenetic mechanisms. (chowdhury2021haploinsufficiencyofprr12 pages 10-11)

Priority studies are:

1. heterozygous and conditional Prr12 knockout mice to test brain, eye, heart, and kidney morphogenesis;
2. zebrafish knockdown/knockout with rescue by human wild-type and variant PRR12;
3. patient-derived neural and retinal organoids to assess dosage-sensitive transcriptional programs;
4. RNA sequencing, chromatin accessibility, DNA methylation, and protein-interaction studies;
5. prospective natural-history and standardized ophthalmology cohorts;
6. functional comparison of truncating and missense alleles and the long versus short isoforms.

Overall assessment

The gene–disease relationship is strongly supported for heterozygous PRR12 loss of function by recurrent de novo truncating alleles, population constraint, a consistent developmental phenotype, and supportive ocular cases. The best-established clinical statistics are developmental impairment in essentially all reported individuals, structural eye defects in 50%, visual impairment in 77% of those assessed, hypotonia in 61%, heart defects in 52%, failure to thrive in 54%, and renal anomalies in 35%. Mechanism beyond haploinsufficiency remains preliminary: developmental nuclear gene regulation and chromatin-associated function are credible hypotheses, but not yet a validated signaling pathway. The major unmet needs are a contemporary expanded cohort, prospective natural history, functional models, formal diagnostic criteria, surveillance guidance, and disease-modifying therapy. (chowdhury2021haploinsufficiencyofprr12 pages 1-2, chowdhury2021haploinsufficiencyofprr12 pages 6-8, chowdhury2021haploinsufficiencyofprr12 pages 10-11)

References

1. (chowdhury2021haploinsufficiencyofprr12 pages 2-2): Fuad Chowdhury, Lei Wang, Mohammed Al-Raqad, David J. Amor, Alice Baxová, Šárka Bendová, Elisa Biamino, Alfredo Brusco, Oana Caluseriu, Nancy J. Cox, Tawfiq Froukh, Meral Gunay-Aygun, Miroslava Hančárová, Devon Haynes, Solveig Heide, George Hoganson, Tadashi Kaname, Boris Keren, Kenjiro Kosaki, Kazuo Kubota, Jennifer M. Lemons, Maria A. Magriña, Paul R. Mark, Marie T. McDonald, Sarah Montgomery, Gina M. Morley, Hidenori Ohnishi, Nobuhiko Okamoto, David Rodriguez-Buritica, Patrick Rump, Zdeněk Sedláček, Krista Schatz, Haley Streff, Tomoko Uehara, Jagdeep S. Walia, Patricia G. Wheeler, Antje Wiesener, Christiane Zweier, Koichi Kawakami, Ingrid M. Wentzensen, Seema R. Lalani, Victoria M. Siu, Weimin Bi, and Tugce B. Balci. Haploinsufficiency of prr12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genetics in Medicine, 23:1234-1245, Jul 2021. URL: https://doi.org/10.1038/s41436-021-01129-6, doi:10.1038/s41436-021-01129-6. This article has 30 citations and is from a highest quality peer-reviewed journal.

2. (chowdhury2021haploinsufficiencyofprr12 pages 1-2): Fuad Chowdhury, Lei Wang, Mohammed Al-Raqad, David J. Amor, Alice Baxová, Šárka Bendová, Elisa Biamino, Alfredo Brusco, Oana Caluseriu, Nancy J. Cox, Tawfiq Froukh, Meral Gunay-Aygun, Miroslava Hančárová, Devon Haynes, Solveig Heide, George Hoganson, Tadashi Kaname, Boris Keren, Kenjiro Kosaki, Kazuo Kubota, Jennifer M. Lemons, Maria A. Magriña, Paul R. Mark, Marie T. McDonald, Sarah Montgomery, Gina M. Morley, Hidenori Ohnishi, Nobuhiko Okamoto, David Rodriguez-Buritica, Patrick Rump, Zdeněk Sedláček, Krista Schatz, Haley Streff, Tomoko Uehara, Jagdeep S. Walia, Patricia G. Wheeler, Antje Wiesener, Christiane Zweier, Koichi Kawakami, Ingrid M. Wentzensen, Seema R. Lalani, Victoria M. Siu, Weimin Bi, and Tugce B. Balci. Haploinsufficiency of prr12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genetics in Medicine, 23:1234-1245, Jul 2021. URL: https://doi.org/10.1038/s41436-021-01129-6, doi:10.1038/s41436-021-01129-6. This article has 30 citations and is from a highest quality peer-reviewed journal.

3. (chowdhury2021haploinsufficiencyofprr12 pages 2-3): Fuad Chowdhury, Lei Wang, Mohammed Al-Raqad, David J. Amor, Alice Baxová, Šárka Bendová, Elisa Biamino, Alfredo Brusco, Oana Caluseriu, Nancy J. Cox, Tawfiq Froukh, Meral Gunay-Aygun, Miroslava Hančárová, Devon Haynes, Solveig Heide, George Hoganson, Tadashi Kaname, Boris Keren, Kenjiro Kosaki, Kazuo Kubota, Jennifer M. Lemons, Maria A. Magriña, Paul R. Mark, Marie T. McDonald, Sarah Montgomery, Gina M. Morley, Hidenori Ohnishi, Nobuhiko Okamoto, David Rodriguez-Buritica, Patrick Rump, Zdeněk Sedláček, Krista Schatz, Haley Streff, Tomoko Uehara, Jagdeep S. Walia, Patricia G. Wheeler, Antje Wiesener, Christiane Zweier, Koichi Kawakami, Ingrid M. Wentzensen, Seema R. Lalani, Victoria M. Siu, Weimin Bi, and Tugce B. Balci. Haploinsufficiency of prr12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genetics in Medicine, 23:1234-1245, Jul 2021. URL: https://doi.org/10.1038/s41436-021-01129-6, doi:10.1038/s41436-021-01129-6. This article has 30 citations and is from a highest quality peer-reviewed journal.

4. (chowdhury2021haploinsufficiencyofprr12 pages 6-8): Fuad Chowdhury, Lei Wang, Mohammed Al-Raqad, David J. Amor, Alice Baxová, Šárka Bendová, Elisa Biamino, Alfredo Brusco, Oana Caluseriu, Nancy J. Cox, Tawfiq Froukh, Meral Gunay-Aygun, Miroslava Hančárová, Devon Haynes, Solveig Heide, George Hoganson, Tadashi Kaname, Boris Keren, Kenjiro Kosaki, Kazuo Kubota, Jennifer M. Lemons, Maria A. Magriña, Paul R. Mark, Marie T. McDonald, Sarah Montgomery, Gina M. Morley, Hidenori Ohnishi, Nobuhiko Okamoto, David Rodriguez-Buritica, Patrick Rump, Zdeněk Sedláček, Krista Schatz, Haley Streff, Tomoko Uehara, Jagdeep S. Walia, Patricia G. Wheeler, Antje Wiesener, Christiane Zweier, Koichi Kawakami, Ingrid M. Wentzensen, Seema R. Lalani, Victoria M. Siu, Weimin Bi, and Tugce B. Balci. Haploinsufficiency of prr12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genetics in Medicine, 23:1234-1245, Jul 2021. URL: https://doi.org/10.1038/s41436-021-01129-6, doi:10.1038/s41436-021-01129-6. This article has 30 citations and is from a highest quality peer-reviewed journal.

5. (chowdhury2021haploinsufficiencyofprr12 pages 8-9): Fuad Chowdhury, Lei Wang, Mohammed Al-Raqad, David J. Amor, Alice Baxová, Šárka Bendová, Elisa Biamino, Alfredo Brusco, Oana Caluseriu, Nancy J. Cox, Tawfiq Froukh, Meral Gunay-Aygun, Miroslava Hančárová, Devon Haynes, Solveig Heide, George Hoganson, Tadashi Kaname, Boris Keren, Kenjiro Kosaki, Kazuo Kubota, Jennifer M. Lemons, Maria A. Magriña, Paul R. Mark, Marie T. McDonald, Sarah Montgomery, Gina M. Morley, Hidenori Ohnishi, Nobuhiko Okamoto, David Rodriguez-Buritica, Patrick Rump, Zdeněk Sedláček, Krista Schatz, Haley Streff, Tomoko Uehara, Jagdeep S. Walia, Patricia G. Wheeler, Antje Wiesener, Christiane Zweier, Koichi Kawakami, Ingrid M. Wentzensen, Seema R. Lalani, Victoria M. Siu, Weimin Bi, and Tugce B. Balci. Haploinsufficiency of prr12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genetics in Medicine, 23:1234-1245, Jul 2021. URL: https://doi.org/10.1038/s41436-021-01129-6, doi:10.1038/s41436-021-01129-6. This article has 30 citations and is from a highest quality peer-reviewed journal.

6. (chowdhury2021haploinsufficiencyofprr12 pages 9-10): Fuad Chowdhury, Lei Wang, Mohammed Al-Raqad, David J. Amor, Alice Baxová, Šárka Bendová, Elisa Biamino, Alfredo Brusco, Oana Caluseriu, Nancy J. Cox, Tawfiq Froukh, Meral Gunay-Aygun, Miroslava Hančárová, Devon Haynes, Solveig Heide, George Hoganson, Tadashi Kaname, Boris Keren, Kenjiro Kosaki, Kazuo Kubota, Jennifer M. Lemons, Maria A. Magriña, Paul R. Mark, Marie T. McDonald, Sarah Montgomery, Gina M. Morley, Hidenori Ohnishi, Nobuhiko Okamoto, David Rodriguez-Buritica, Patrick Rump, Zdeněk Sedláček, Krista Schatz, Haley Streff, Tomoko Uehara, Jagdeep S. Walia, Patricia G. Wheeler, Antje Wiesener, Christiane Zweier, Koichi Kawakami, Ingrid M. Wentzensen, Seema R. Lalani, Victoria M. Siu, Weimin Bi, and Tugce B. Balci. Haploinsufficiency of prr12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genetics in Medicine, 23:1234-1245, Jul 2021. URL: https://doi.org/10.1038/s41436-021-01129-6, doi:10.1038/s41436-021-01129-6. This article has 30 citations and is from a highest quality peer-reviewed journal.

7. (chowdhury2021haploinsufficiencyofprr12 pages 10-11): Fuad Chowdhury, Lei Wang, Mohammed Al-Raqad, David J. Amor, Alice Baxová, Šárka Bendová, Elisa Biamino, Alfredo Brusco, Oana Caluseriu, Nancy J. Cox, Tawfiq Froukh, Meral Gunay-Aygun, Miroslava Hančárová, Devon Haynes, Solveig Heide, George Hoganson, Tadashi Kaname, Boris Keren, Kenjiro Kosaki, Kazuo Kubota, Jennifer M. Lemons, Maria A. Magriña, Paul R. Mark, Marie T. McDonald, Sarah Montgomery, Gina M. Morley, Hidenori Ohnishi, Nobuhiko Okamoto, David Rodriguez-Buritica, Patrick Rump, Zdeněk Sedláček, Krista Schatz, Haley Streff, Tomoko Uehara, Jagdeep S. Walia, Patricia G. Wheeler, Antje Wiesener, Christiane Zweier, Koichi Kawakami, Ingrid M. Wentzensen, Seema R. Lalani, Victoria M. Siu, Weimin Bi, and Tugce B. Balci. Haploinsufficiency of prr12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genetics in Medicine, 23:1234-1245, Jul 2021. URL: https://doi.org/10.1038/s41436-021-01129-6, doi:10.1038/s41436-021-01129-6. This article has 30 citations and is from a highest quality peer-reviewed journal.

8. (chowdhury2021haploinsufficiencyofprr12 pages 3-4): Fuad Chowdhury, Lei Wang, Mohammed Al-Raqad, David J. Amor, Alice Baxová, Šárka Bendová, Elisa Biamino, Alfredo Brusco, Oana Caluseriu, Nancy J. Cox, Tawfiq Froukh, Meral Gunay-Aygun, Miroslava Hančárová, Devon Haynes, Solveig Heide, George Hoganson, Tadashi Kaname, Boris Keren, Kenjiro Kosaki, Kazuo Kubota, Jennifer M. Lemons, Maria A. Magriña, Paul R. Mark, Marie T. McDonald, Sarah Montgomery, Gina M. Morley, Hidenori Ohnishi, Nobuhiko Okamoto, David Rodriguez-Buritica, Patrick Rump, Zdeněk Sedláček, Krista Schatz, Haley Streff, Tomoko Uehara, Jagdeep S. Walia, Patricia G. Wheeler, Antje Wiesener, Christiane Zweier, Koichi Kawakami, Ingrid M. Wentzensen, Seema R. Lalani, Victoria M. Siu, Weimin Bi, and Tugce B. Balci. Haploinsufficiency of prr12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genetics in Medicine, 23:1234-1245, Jul 2021. URL: https://doi.org/10.1038/s41436-021-01129-6, doi:10.1038/s41436-021-01129-6. This article has 30 citations and is from a highest quality peer-reviewed journal.

9. (chowdhury2021haploinsufficiencyofprr12 pages 5-6): Fuad Chowdhury, Lei Wang, Mohammed Al-Raqad, David J. Amor, Alice Baxová, Šárka Bendová, Elisa Biamino, Alfredo Brusco, Oana Caluseriu, Nancy J. Cox, Tawfiq Froukh, Meral Gunay-Aygun, Miroslava Hančárová, Devon Haynes, Solveig Heide, George Hoganson, Tadashi Kaname, Boris Keren, Kenjiro Kosaki, Kazuo Kubota, Jennifer M. Lemons, Maria A. Magriña, Paul R. Mark, Marie T. McDonald, Sarah Montgomery, Gina M. Morley, Hidenori Ohnishi, Nobuhiko Okamoto, David Rodriguez-Buritica, Patrick Rump, Zdeněk Sedláček, Krista Schatz, Haley Streff, Tomoko Uehara, Jagdeep S. Walia, Patricia G. Wheeler, Antje Wiesener, Christiane Zweier, Koichi Kawakami, Ingrid M. Wentzensen, Seema R. Lalani, Victoria M. Siu, Weimin Bi, and Tugce B. Balci. Haploinsufficiency of prr12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities. Genetics in Medicine, 23:1234-1245, Jul 2021. URL: https://doi.org/10.1038/s41436-021-01129-6, doi:10.1038/s41436-021-01129-6. This article has 30 citations and is from a highest quality peer-reviewed journal.

Artifacts

• Edison artifact artifact-00